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https://www.readbyqxmd.com/read/29898960/antibody-inhibition-of-properdin-prevents-complement-mediated-intravascular-and-extravascular-hemolysis
#1
Damodar Gullipalli, Fengkui Zhang, Sayaka Sato, Yoshiyasu Ueda, Yuko Kimura, Madhu Golla, Takashi Miwa, Jianxiang Wang, Wen-Chao Song
Paroxysmal nocturnal hemoglobinuria (PNH) is a serious blood disorder characterized by dysregulated complement activation on blood cells. Eculizumab, the current standard therapy and a humanized anti-C5 mAb, relieves anemia and thrombosis symptoms of PNH patients by preventing complement-dependent intravascular hemolysis (IVH). However, up to 20% of PNH patients on long-term eculizumab treatment still suffer from significant anemia and are transfusion dependent because of extravascular hemolysis (EVH) of C3-opsonized PNH erythrocytes...
June 13, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29895552/prevention-of-fatal-c3-glomerulopathy-by-recombinant-complement-receptor-of-the-ig-superfamily
#2
Xiaoxu Wang, Menno Van Lookeren Campagne, Kenneth J Katschke, Damodar Gullipalli, Takashi Miwa, Yoshiyasu Ueda, Yuan Wang, Matthew Palmer, Guolan Xing, Wen-Chao Song
Background C3 glomerulopathy (C3G) is a life-threatening kidney disease caused by dysregulation of the alternative pathway of complement (AP) activation. No approved specific therapy is available for C3G, although an anti-C5 mAb has been used off-label in some patients with C3G, with mixed results. Thus, there is an unmet medical need to develop other inhibitors of complement for C3G. Methods We used a murine model of lethal C3G to test the potential efficacy of an Fc fusion protein of complement receptor of the Ig superfamily (CRIg-Fc) in the treatment of C3G...
June 12, 2018: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/29867915/human-properdin-modulates-macrophage-mycobacterium-bovis-bcg-interaction-via-thrombospondin-repeats-4-and-5
#3
Maha Ahmed Al-Mozaini, Anthony G Tsolaki, Munirah Abdul-Aziz, Suhair M Abozaid, Mohammed N Al-Ahdal, Ansar A Pathan, Valarmathy Murugaiah, Evgeny M Makarov, Anuvinder Kaur, Robert B Sim, Uday Kishore, Lubna Kouser
Mycobacterium tuberculosis can proficiently enter macrophages and diminish complement activation on its cell surface. Within macrophages, the mycobacterium can suppress macrophage apoptosis and survive within the intracellular environment. Previously, we have shown that complement regulatory proteins such as factor H may interfere with pathogen-macrophage interactions during tuberculosis infection. In this study, we show that Mycobacterium bovis BCG binds properdin, an upregulator of the complement alternative pathway...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29858280/blocking-properdin-prevents-complement-mediated-hemolytic-uremic-syndrome-and-systemic-thrombophilia
#4
Yoshiyasu Ueda, Takashi Miwa, Damodar Gullipalli, Sayaka Sato, Daisuke Ito, Hangsoo Kim, Matthew Palmer, Wen-Chao Song
Background Properdin (P) is a positive regulator of the alternative pathway of complement activation. Although P inhibition is expected and has been shown to ameliorate the alternative pathway of complement-mediated tissue injury in several disease models, it unexpectedly exacerbated renal injury in a murine model of C3 glomerulopathy. The role of P in atypical hemolytic uremic syndrome (aHUS) is uncertain. Methods We blocked P function by genetic deletion or mAb-mediated inhibition in mice carrying a factor H (FH) point mutation, W1206R (FHR/R ), that causes aHUS and systemic thrombophilia with high mortality...
June 1, 2018: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/29741515/-assessment-of-health-information-available-online-regarding-meningococcal-b-vaccine-recommendations
#5
Ignacio Hernández-García, Teresa Giménez-Júlvez
OBJECTIVE: The quality of health information online is a concern to governments and users. Our objective was to determine the extent to which the information available online regarding meningococcal B vaccine recommendations adhere to the guidelines of the Spanish Ministry of Health. METHODS: Cross-sectional study carried out in April 2017. The study assessed adherence of information regarding vaccine recommendations to official guidelines. The information was collected via Google with 20 keywords...
May 11, 2018: Revista Española de Salud Pública
https://www.readbyqxmd.com/read/29525356/looking-back-on-the-alternative-complement-pathway
#6
REVIEW
Peter J Lachmann
The alternative pathway of complement originated from the Properdin pathway originally described by the Pillemer laboratory in the 1950s. This work generated great controversy and it took several decades for a consensus on its components, its reaction sequence and its functions to emerge. This paper reviews this history and attempts to clarify some of the ambiguities that remain.
March 6, 2018: Immunobiology
https://www.readbyqxmd.com/read/29483907/human-properdin-opsonizes-nanoparticles-and-triggers-a-potent-pro-inflammatory-response-by-macrophages-without-involving-complement-activation
#7
Lubna Kouser, Basudev Paudyal, Anuvinder Kaur, Gudrun Stenbeck, Lucy A Jones, Suhair M Abozaid, Cordula M Stover, Emmanuel Flahaut, Robert B Sim, Uday Kishore
Development of nanoparticles as tissue-specific drug delivery platforms can be considerably influenced by the complement system because of their inherent pro-inflammatory and tumorigenic consequences. The complement activation pathways, and its recognition subcomponents, can modulate clearance of the nanoparticles and subsequent inflammatory response and thus alter the intended translational applications. Here, we report, for the first time, that human properdin, an upregulator of the complement alternative pathway, can opsonize functionalized carbon nanotubes (CNTs) via its thrombospondin type I repeat (TSR) 4 and 5...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29459849/widely-used-commercial-elisa-does-not-detect-precursor-of-haptoglobin2-but-recognizes-properdin-as-a-potential-second-member-of-the-zonulin-family
#8
Lucas Scheffler, Alyce Crane, Henrike Heyne, Anke Tönjes, Dorit Schleinitz, Christian H Ihling, Michael Stumvoll, Rachel Freire, Maria Fiorentino, Alessio Fasano, Peter Kovacs, John T Heiker
Background: There is increasing evidence for the role of impaired intestinal permeability in obesity and associated metabolic diseases. Zonulin is an established serum marker for intestinal permeability and identical to pre-haptoglobin2. Here, we aimed to investigate the relationship between circulating zonulin and metabolic traits related to obesity. Methods: Serum zonulin was measured by using a widely used commercial ELISA kit in 376 subjects from the metabolically well-characterized cohort of Sorbs from Germany...
2018: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/29446739/role-of-complement-properdin-in-renal-ischemia-reperfusion-injury
#9
Zinah Zwaini, Houyong Dai, Cordula Stover, Bin Yang
Renal Ischemia-Reperfusion Injury (IRI) is one of the main causes of Acute Kidney Injury (AKI), and may lead to chronic kidney disease. The high mortality rate of AKI has not changed in the last 5 decades due to non-recognition, nephrotoxin exposure, delayed diagnosis and lack of specific intervention. Complement activation plays important roles in IRI-induced AKI because of its association with immunity, inflammation, cell death and tissue repair. Nevertheless, the role of complement properdin, the sole positive regulator of the alternative pathway, in IRI-induced AKI has not been well defined...
2017: Current Gene Therapy
https://www.readbyqxmd.com/read/29376659/parsimonious-charge-deconvolution-for-native-mass-spectrometry
#10
Marshall Bern, Tomislav Caval, Yong J Kil, Wilfred Tang, Christopher Becker, Eric Carlson, Doron Kletter, K Ilker Sen, Nicolas Galy, Dominique Hagemans, Vojtech Franc, Albert J R Heck
Charge deconvolution infers the mass from mass over charge (m/z) measurements in electrospray ionization mass spectra. When applied over a wide input m/z or broad target mass range, charge-deconvolution algorithms can produce artifacts, such as false masses at one-half or one-third of the correct mass. Indeed, a maximum entropy term in the objective function of MaxEnt, the most commonly used charge deconvolution algorithm, favors a deconvolved spectrum with many peaks over one with fewer peaks. Here we describe a new "parsimonious" charge deconvolution algorithm that produces fewer artifacts...
March 2, 2018: Journal of Proteome Research
https://www.readbyqxmd.com/read/29367209/the-complement-c3a-c3ar-axis-promotes-development-of-thoracic-aortic-dissection-via-regulation-of-mmp2-expression
#11
Weihong Ren, Yan Liu, Xuerui Wang, Chunmei Piao, Youcai Ma, Shulan Qiu, Lixin Jia, Boya Chen, Yuan Wang, Wenjian Jiang, Shuai Zheng, Chang Liu, Nan Dai, Feng Lan, Hongjia Zhang, Wen-Chao Song, Jie Du
Thoracic aortic dissection (TAD), once ruptured, is devastating to patients, and no effective pharmaceutical therapy is available. Anaphylatoxins released by complement activation are involved in a variety of diseases. However, the role of the complement system in TAD is unknown. We found that plasma levels of C3a, C4a, and C5a were significantly increased in patients with TAD. Elevated circulating C3a levels were also detected in the developmental process of mouse TAD, which was induced by β-aminopropionitrile monofumarate (BAPN) treatment, with enhanced expression of C1q and properdin in mouse dissected aortas...
March 1, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29279246/complement-system-biomarkers-in-first-episode-psychosis
#12
Maja Kopczynska, Wioleta Zelek, Samuel Touchard, Fiona Gaughran, Marta Di Forti, Valeria Mondelli, Robin Murray, Michael C O'Donovan, B Paul Morgan
Several lines of evidence implicate immunological/inflammatory factors in development of schizophrenia. Complement is a key driver of inflammation, and complement dysregulation causes pathology in many diseases. Here we explored whether complement dysregulation occurred in first episode psychosis (FEP) and whether this provides a source of biomarkers. Eleven complement analytes (C1q, C3, C4, C5, factor B [FB], terminal complement complex [TCC], factor H [FH], FH-related proteins [FHR125], Properdin, C1 inhibitor [C1inh], soluble complement receptor 1 [CR1]) plus C-reactive protein (CRP) were measured in serum from 136 first episode psychosis (FEP) cases and 42 mentally healthy controls using established in-house or commercial ELISA...
December 23, 2017: Schizophrenia Research
https://www.readbyqxmd.com/read/29245944/extracellular-vesicles-from-kshv-infected-endothelial-cells-activate-the-complement-system
#13
Hyungtaek Jeon, Seung-Min Yoo, Hyo Sun Choi, Ji Young Mun, Hee-Gyoo Kang, Jiyeong Lee, Jinsung Park, Shou-Jiang Gao, Myung-Shin Lee
Extracellular vesicles (EVs), released by cells, are associated with cell-to-cell communication and regulate various cellular processes. EVs draw parallels with viruses for their similar structures and functions. Increasing evidences from recent studies indicate that cells infected with viruses release a variety of EVs. Delineating the functions and mechanisms of EVs released during virus infection is essential for understanding the molecular basis of viral infection and replication as well as associated pathogenesis...
November 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/29207081/increased-serum-protein-levels-by-yuanshi-shengmai-chenggu-tablet-in-treatment-of-avascular-osteonecrosis-of-the-femoral-head
#14
Jianchun Zeng, Peng Deng, Jie Li, Wenjun Feng, Jinlun Chen, Yirong Zeng
The traditional Chinese medicine (TCM) Yuanshi Shengmai Chenggu Tablet is used for treating the common orthopedic disease, hormone‑induced avascular necrosis of the femoral head (ANFH) in China. However, its underlying mechanism and the changes induced in the treatment of ANFH remain to be fully elucidated. In the present study, through the use of isobaric Tag for Relative and Absolute Quantitation and multiple reaction monitoring quantifications, corticosteroid‑induced femoral head necrosis and the effects of treatment with Yuanshi Shengmai Chenggu Tablet were examined...
February 2018: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29174517/longitudinal-associations-of-the-alternative-and-terminal-pathways-of-complement-activation-with-adiposity-the-codam-study
#15
Ying Xin, Elisabeth Hertle, Carla J H van der Kallen, Casper G Schalkwijk, Coen D A Stehouwer, Marleen M J van Greevenbroek
OBJECTIVE: To investigate longitudinal associations of components of the alternative (C3, C3a, Bb, factor D [FD], factor H [FH], and properdin) and the terminal complement pathway (C5a, sC5b-9) with adiposity. METHODS: A prospective human cohort study (n=574 at baseline, n=489 after 7 years follow-up) was analyzed. Generalized estimating equations were used to evaluate the longitudinal associations between complement components (standardized values) and adiposity (main outcome BMI [kg/m2 ])...
November 21, 2017: Obesity Research & Clinical Practice
https://www.readbyqxmd.com/read/29167939/the-properdin-pathway-an-alternative-activation-pathway-or-a-critical-amplification-loop-for-c3-and-c5-activation
#16
REVIEW
Richard A Harrison
This review is not intended to cover in detail all aspects of the discovery and evolution of our understanding of the "alternative pathway" of complement activation, there are many excellent reviews that do this (see Fearon (CRC Crit Rev Immunol 1:1-32, 1979), Pangburn and Müller-Eberhard (Springer Semin Immunopathol 7:163-192, 1984)), but instead to give sufficient background for current concepts to be put in context. The prevailing textbook view, of components having a primary role as an alternative "pathway" for C3 activation, is challenged, with an argument developed for the primary role of the system being that of providing a surface-dependent amplification loop for both C3 and C5 activation...
January 2018: Seminars in Immunopathology
https://www.readbyqxmd.com/read/29128668/inhibition-of-the-complement-system-by-saliva-of-anopheles-nyssorhynchus-aquasalis
#17
Antonio Ferreira Mendes-Sousa, Vladimir Fazito Vale, Daniel Costa Queiroz, Adalberto Alves Pereira-Filho, Naylene Carvalho Sales da Silva, Leonardo Barbosa Koerich, Luciano Andrade Moreira, Marcos Horácio Pereira, Maurício Roberto Sant'Anna, Ricardo Nascimento Araújo, John Andersen, Jesus Gilberto Valenzuela, Nelder Figueiredo Gontijo
Anopheline mosquitoes are vectors of malaria parasites. Their saliva contains anti-hemostatic and immune-modulator molecules that favor blood feeding and parasite transmission. In this study, we describe the inhibition of the alternative pathway of the complement system (AP) by Anopheles aquasalis salivary gland extracts (SGE). According to our results, the inhibitor present in SGE acts on the initial step of the AP blocking deposition of C3b on the activation surfaces. Properdin, which is a positive regulatory molecule of the AP, binds to SGE...
January 2018: Insect Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/28912782/the-sand-fly-salivary-protein-lufaxin-inhibits-the-early-steps-of-the-alternative-pathway-of-complement-by-direct-binding-to-the-proconvertase-c3b-b
#18
Antonio F Mendes-Sousa, Vladimir Fazito do Vale, Naylene C S Silva, Anderson B Guimaraes-Costa, Marcos H Pereira, Mauricio R V Sant'Anna, Fabiano Oliveira, Shaden Kamhawi, José M C Ribeiro, John F Andersen, Jesus G Valenzuela, Ricardo N Araujo
Saliva of the blood feeding sand fly Lutzomyia longipalpis was previously shown to inhibit the alternative pathway (AP) of the complement system. Here, we have identified Lufaxin, a protein component in saliva, as the inhibitor of the AP. Lufaxin inhibited the deposition of C3b, Bb, Properdin, C5b, and C9b on agarose-coated plates in a dose-dependent manner. It also inhibited the activation of factor B in normal serum, but had no effect on the components of the membrane attack complex. Surface plasmon resonance (SPR) experiments demonstrated that Lufaxin stabilizes the C3b-B proconvertase complex when passed over a C3b surface in combination with factor B...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28864337/complement-genomics-and-antibody-mediated-rejection-in-heart-recipients
#19
EDITORIAL
Javier Carbone
In this issue of the Journal of Heart and Lung Transplantation, Marrón-Liñares et al report the results of an interesting study in which they evaluated 51 genes associated with the complement pathway in a small number of heart recipients to explore their relationship with antibody-mediated rejection (AMR). Next-generation sequencing was used in 46 heart transplant recipients (23 with AMR and 23 without AMR). The authors identified a significant association of 2 single-nucleotide polymorphisms with the absence or presence of AMR, respectively, p...
April 2018: Journal of Heart and Lung Transplantation
https://www.readbyqxmd.com/read/28712854/c5-nephritic-factors-drive-the-biological-phenotype-of-c3-glomerulopathies
#20
Maria-Chiara Marinozzi, Sophie Chauvet, Moglie Le Quintrec, Morgane Mignotet, Florent Petitprez, Christophe Legendre, Mathilde Cailliez, Georges Deschenes, Michel Fischbach, Alexandre Karras, Francois Nobili, Christine Pietrement, Marie-Agnes Dragon-Durey, Fadi Fakhouri, Lubka T Roumenina, Veronique Fremeaux-Bacchi
C3 Glomerulopathies, which include Dense Deposit Disease and C3 Glomerulonephritis, are associated with genetic and acquired dysregulation of the C3 convertase alternative pathway of complement. The potential role of the activation of the C5 convertase has not been studied extensively. Here we analyzed IgG samples from patients with C3 Glomerulopathies to identify circulating autoantibodies that stabilize the C3 alternative pathway (C3 Nephritic Factors) as well as C5 convertases (C5 Nephritic Factors), thus preventing decay of these enzyme complexes...
November 2017: Kidney International
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